Kyle J. Norton (Scholar and Master of Nutrients, all right reserved)Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Musculoskeletal disorders (MSDs) are medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. According to a community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home, musculoskeletal pain was reported by 57% of those interviewed(*).
Types of Musculo-Skeletal disorders in elder
1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia
Gout
Gout mostly effected one joint is an acute and recurrent condition of arthritis as a result of uric acid building up in blood, inducing joint inflammation.
Symptoms
In the study carry out a cross-sectional survey on prevalence of musculoskeletal symptoms, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout, Dr. Dai SM, and the research team at the Second Military Medical University, in the interviewe a total of 6584 adults (3394 women, 3190 men) with the response rate of 86.6%. showed that symptoms occurred more frequently in the following sites: knee 7.0% (95% CI 6.4-7.6%), lower back 5.6% (95% CI 5.0-6.2%), shoulder 4.7% (95% CI 4.2-5.2%), and neck 2.4% (95% CI 2.0-2.8%). Women complained of rheumatic symptoms more frequently than men. The standardized rates of RA, AS, gout, symptomaticknee osteoarthritis, and soft tissue rheumatism were 0.28% (95% CI 0.15-0.41%), 0.11% (95% CI 0.03-0.19%), 0.22% (95% CI 0.11-0.33%), 4.1% (95% CI 3.6-4.6%), and 3.4% (95% CI 3.0-3.8%), respectively(1a).
Most frequent symptoms of gout as a result of tophus(4), according to studies including
1. Warmth(1), pain(1), particular endpoint pain(2), swelling(1), erythema(1), and extreme tenderness(2)(called podagra. when it effects the big toe), according to the Cadence Physician Group/Orthopaedics(1)
2. Very red or purplish skin on the affect joint(5)
3. Reduced movement of affect joint and big toe, according ot the study by the Auckland University of Technology, walking shoes with good footwear characteristics can influence plantar pressure values and encourage a more efficient heel to toe gait pattern in people with gout(3).
4. Induced skin itching and peeling when the affect joint begins to heal(5)
5. Intractable back pain and fever if it a spinal gout(6).
In fact, symptoms are quite noticeable, you may feel well when you go to bed but wake up during the night with intense pain in one or few joints and sometime with fever. The symptoms may go away in a few days, but can return from time to time. Chronic gout can cause lumps(4) below the skin around the affect areas.
Causes and risk factors
A. Causes
The causes of gout is as the result of high levels of uric acid in the body that can lead to forming of crystals causes of inflammation due to your body can not get rid of uric acid or have made too much uric acid(4). Reduced intake of meats and seafood and foods containing higher levels of uric acid, such as alcoholic beverages, especially beer, and drinks sweetened with fruit sugar (fructose) may be necessary(7)(8).
According to the New York University School of Medicine/Langone Medical Center, the prevalence of gout and hyperuricemia has increased dramatically during the last several decades, to the point that gout is the most common inflammatory arthritis in the United States, affecting approximately 8 million Americans(9) and contributing to great numbers of hypertension, chronic kidney disease, and cardiovascular disease(9).
B. Risk factors
1. Improper diet
If you body can not get rid uric acid quickly, intake foods with high levels of purine such as Alcohol, Beverages, Beer, Anchovies, Smelt, Fish, Eggs, Herring, Mackerel, Sardine, Sweetbread, Liver, Kidney, etc., is at increased risk of gout(7)(8)(10). Several dietary factors increased the risk of incident gout, including meat intake, seafood intake, sugar sweetened soft drinks, and consumption of foods high in fructose(10).
2. Alcohol consumption
Dr. Singh JA and scientists at the Birmingham VA Medical Centre, indicated, of the 751 titles and abstracts, 53 studies met the criteria and were included in the review. Several risk factors were studied. Alcohol consumption increased the risk of incident gout, especially beer and hard liquor(10)(7).
Others suggested that combined with their activities as urinate transporters and their strong associations with serum uric acid concentrations,
3. Medical conditions
Hypertension, renal insufficiency, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, diabetes are associated to increased risk of gout(10). Patient with Chronic kidney disease are at higher risk of gout as a result of Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD(11). Distinct group differences by content of uric acid seem to arise from early onset of chronic renal failure in women.
4. Medication
Gout is also drug-related(21). Thiazide and loop diuretics users are at increased risk of gout(12)(10), according to Johns Hopkins University Bloomberg School of Public Health.
5. Race
Some ethnic groups are particularly susceptible to gout, probaby due to genetic predisposition(13)(14).
6. Age and sex are associated to risk of the develop of gout(14)(15).
7. Genetics
GLUT9 and ABCG2 appeared to be important modulators of uric acid levels and likely of the risk of gout. Together with a growing list of environmental risk factors, these genetic data add considerably to our understanding of the pathogenesis of hyperuricemia and gout(16)(17)(19).
8. Family history
Accoridng to the total of 543 cases of juvenile gout from the Ho-Ping Gout Database, and 5269 gouty cases with onset age of 40 to 50 years, family history is associated to increased risk of gout(18)(19)
9. Obesity, over weight, weight change
Obesity and overweight are associated with a higher risk of incident gout and/or gout flare(10)(19).
Higher adiposity and weight gain are strong risk factors for gout in men, while weight loss is protective(5).
10. Menopause
Early menopause is associated with a higher risk of incident gout and/or gout flare(10). According to the16 years of follow-up (1 240 231 person-years), 1703 incident gout cases, conducted by the Taipei Municipal Hospital Gout Research Group, compared with premenopausal women, postmenopausal women had a higher risk of incident gout. Risk of gout is decreased among postmenopausal hormone users(22).
11. Recent surgery or trauma
According to Cleveland Clinic, risk of early postoperative gout is higher after bariatric surgery in comparison of patients undergoing other procedures(23)(24). There is a report of monoarticular gout following trauma in Medical College of Wisconsin literature(25).
Diseases associated with Gout
According to the UK Gout Society, diseases associated to gout may include
1. Hypertension
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. High blood pressure means raising pressure in your heart.If it stays high over time it can damage the body in many ways.
Dr, Gibson TJ said, "gout are associated with hypertension and chronic kidney disease is well established" and "(many medication such as Losartan may possess mild uricosuric properties and therefore has a role in treating hypertensive patients with gout"(26).
Western medication such as hydrochlorothiazide (HCTZ) and chlorthalidone (CTD), according to the University of Missouri, are effective used for treatment of hypertension in gout patients(27) with certain unwanted side effects.
Diet rich in fruits and vegetable and reduced intake of red meat, saturated fat and trans fat has shown to attenuated risk of hypertension(28). Recent study showed that celery(29) intake used conjunction with berries(30) and green tea(31) may be the potential drink for prevention and treatment of hypertension in patients with gout.
For more information visit: The Smoothies of celery, apple and green tea for prevention and treatment of Hypertension(32)
2. Renal insufficiency
Patients with gout are associated to chronic kidney disease has been well documented in epidemiological literature(26). The joint study led by the Keele University suggested, "Chronic kidney disease and nephrolithiasis are commonly found amongst patients with gout. Gout is independently associated with both chronic kidney disease and nephrolithiasis. Patients with gout should be actively screened for chronic kidney disease and its consequences"(33).
Dr. Krishnan E said, "Chronic kidney disease manifesting as reduced glomerular function or as presence of blood or protein in the urine increases the risk of incident gout"(34).
Chronic Kidney disease is defined as a condition of the progression loss of kidney function over period of many years. Stage of chronic kidney disease according to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQ).
In the review of literature from data base of PubMed, Brazil Nut(35)(36), Flax Seed(37) and Honey(38)(39) found effectively in treatment of renal insufficiency back by recent studies from some well known institutions may serve as cornerstones of pharmaceutical target for further studies as well as a potential medication for treatment of Chronic Kidney disease in patient with gout. For more information, please visit The Impossible Smoothie of Brazil Nut, Flax Seed and Honey For Prevention and Treatment of Chronic Kidney disease(40).
3. Hypertriglyceridemia
Unhealthy diet such as typical American diet with high in saturated and trans fat and lower intake of vegetables and fruits has been found to associated to hypertriglyceridemia in epiodemilogical literature in data bases of PubMed(41)(42)(43), particular to hypertriglyceridemia in men(46).
In the searching of the association of hypertriglyceridemia in patients with gout, according to the Osaka University Medical School, there is a close correlation between the degree of uric acid production and triglyceride (TG) metabolism in 148 male subjects with primary gout(45).
Dr. Naito HK and Dr. Mackenzie AH. insisted, " diet and, possibly, defective clearance of triglycerides may be etiologic factors associated with the abnormal serum triacylglycerol (triglyceride) and lipoprotein concentrations in these individuals"(44).
According to the Korean National Health and Nutrition Examination Surveys (KNHANES) 2007-2009, supported the potential beneficial role of vegetables and fruits consumption to reduce blood triglyceride levels in Asian populations(47).
Furthermore, High-fat ketogenic diets, the only treatment available for Glut1 deficiency (Glut1D) as od today, according to joint study led by the Children's Hospital Aschaffenburg Alzenau after 3 years intake, showed a gradual increase of blood lipids, followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL)(48).
4. Hypercholesterolemia
Unhealthy diet such as typical American diet with high in satyrated and trans fat and lower intake of vegetables and fruits has been found to associated to Hypertriglyceridemia and Hypercholesterolemia in epidemiological literature in data bases of PubMed(41)(42)(43).
Dr. Tu FY and colleagues of some well known institutions in Taiwan, according to the data from the Taiwan national health insurance database for 2004 to 2006, showed that hypercholesterolemia, were the common comorbidities of gout(56).
Furthermore, the association of gout and hypercholesterolemia may be due to poor quality of life style implications(59) such as alcohol intake(57) as well as dietary low in vegetables and fruits(58)
Recent studies suggested that avocado(49)(50), Almond(51)(52) and green tea(53)(54) may consist a therapeutic values used combination for reduced risk and treatment of high blood cholesterol in patients with gout.
For more information of above effectiveness, please visit, The Smoothie of avocado, Almond and green tea for prevention and treatment of Hyperlipidemia(High blood Cholesterol)(55).
5. Hyperuricemia
Hyperuricemia, a condition with over expression of uric acid in the blood through liver most often found in patients with gout. According to Dr. Li YM. said, "It has been widely accepted that the increase in the level of uric acid significantly raises the risks of gout, cardiovascular disease, and type 2 diabetes."
It is acceptance epidemiological studies that high fruit and soybean products dietary intervention could be an effective alternative to a standard diet for achieving clinically important reductions in SUA for asymptomatic hyperuricemia patients(61). And major dietary patterns such as animal products and fried food are associated to risk of hyperuricemia(62).
According to the Chiang Mai University, green tea extract (GTE) also promoted hypouricemic and anti gout effects through modestly lowering serum uric acid (SUA) level and decreasing uric acid clearance(63).
Reduced intake of food with rich purine, alcohol intake as well as controlling obesity and blood pressure, improving the status of lipid metabolic disorder together with programs as hypertension control etc.(64).
6. Diabetes
Diabetes is a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.
According to the University of Chicago, diabetic gout patients were older, more frequently female, and had longer gout duration(65).It is said that conventional treatment with 80 mg febuxostat may be more efficacious in female gout subjects with high rates of comorbidities in comparison of commonly prescribed doses of allopurinol(66).
Dr. Donath MY said, " an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome(particular diabetes) such as psoriasis, gout and rheumatic arthritis"(67).
Recent studies back by renowned institution suggested that Cinnamon(69), Whole Food Papaya(70) and Green Tea(71) reduced Risk and Treatment of Diabetes through their effects in improved fasting blood glucose levels and glucose tolerance without altering the insulin secretion and in regulation of metabolism (carbohydrate, lipid, protein))-medicated glucose and lipid metabolism(68).
7. Obesity
Obesity, one of the disease of metabolic syndrome is a medical condition of excess body fat accumulated overtime, while overweight is a condition of excess body weight relatively to the height.
According to the joint study led by the Catholic University of Korea, gout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities(72). And General obesity in women may potentiate an sUA effect for gout development in the study of a total of 261,500 person-years conducted by the China Medical University(73).
Recent studies conducted by some renowned institutions suggested that green tea(75)(76), avocado and(77) blueberry(78)979) may be a potent drink for reduced weight and treatment of overweight and obese subjects.
People who are at increased risk of overweight due to family history, gene mutation, .....should drink at least one serving daily and overweight and obese people should drink the smoothie as much as they can depending to digestive toleration.
Change of life style and diet pattern are also recommended(74).
8. Heart diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of tuncontrolled diet with high levels of saturated fat and trans fat. According to study, risk of heart attached is increased in older women with gout(80).
In a total of 8,656,413 participants with a total of 1000 MI events included in the study conducted by Taizhou Municipal Hospital, patients with gout have an increased risk of myocardial infarction(81).
Recent studies conducted by some well known institutions suggested that the combination of Blueberry(82), Avocado(83) were found to have a potential effect for Reduced Risk and Treatment of Heart Disease. and recommended that People who are at increased of heart disease due to family history, obesity, gout.....should drink at least one serving daily and people with heart disease should drink no more than 4 servings a day, depending to digestive toleration.
Change of life style and diet pattern are also recommended(84).
9. Stroke
Besides cancer and heart diseases, stroke is the third leading cause of death. Approximate 1/4 of all stroke victims die as a direct result of the stroke or it's complications. Stroke is caused by uncontrolled diet that is high in saturated and trans fats resulting in cholesterol build up in the arteries and high blood pressure.
In the review of all-England dataset included 202 033 hospital patients and all-England national linked dataset of hospital admissions and death records from 1999 to 2011, the University of Oxford, strongly confirmed that gout was associated with increased risk of stroke(85).
Dr. Grassi W and Dr. De Angelis R. in the analyzed clinical features of gout. found that gouty patients often have a medical history, including stroke, resulting with a poor overall quality of life(86).
This finding of the effectiveness of Green Tea(87) and coffee(88) and blueberry(89) phytochemicals in recent studies by some respectable institutions may serve as cornerstones of pharmaceutical target for further studies in production of a potential medication for reduced risk treatment of stroke with little or no adverse effects.
If you need more information of above finding, please visit The incredible smoothie Green Tea, Coffee and Blueberry for reduced risk and treatment of Stroke(90)
11. Peripheral vascular(artery) disease
Peripheral vascular disease is a condition of poor circulation of blood, affecting the functions of heart and brain. Because of of its implication involving risk of myocardial infarction, stroke, and cardiovascular death and impaired quality of life, some researchers suggested of the importance in identified patients with PAD have become necessary(91). According to the a large cohort of primary care patients, patients with gout are associated to increase risk of vascular disease, particular in female patients with gout(92).
Dr. Baker JF and colleagues at the University of Pennsylvania said, " in multivariate model, a history of gout was associated with an odds ratio of 1.33. Serum uric acid level is independently associated with a higher (but statistically nonsignificant) risk of PAD"(93).
In the study involved classical risk factors and rheological profile of patients suffering from vascular disease of. 364 patients out of a total of 2,498 individuals suffered from vascular disease, the University of Saarland study insisted that patients with gout and metabolic syndrome are associated to elevated risk of peripheral vascular disease(94).
12. Psoriasis
Psoriasis is an autoimmune diseases induced abnormal skin path with expression of redness, itchy, and scaly. According to the joint study led by the University of Trieste, the increased incidence of a large number of diseases which share an inflammatory origin probably due to the pro-inflammatory cytokine spillover from active psoriatic lesions leading to a large inflammation on distant tissues(95).
Methotrexate, a conventional medicine may be an effective therapy for extensive and severe forms of psoriasis if patients are selected carefully and monitored regularly in the dose of <15-20 mg/week(96) Dr. Haustein UF and Dr. Rytter M. insisted(96).
According to the joint study led by the Brigham and Women's Hospital and Harvard Medical School, Boston, individuals with psoriasis have increased blood levels of uric acid. In the documented 2217 incident cases of gout during follow-up. Psoriasis was associated with an increased risk of subsequent gout with a multivariate HR of 1.71(97).
Dr. Lai YC and Dr.Yew YW said, " A raised serum uric acid level may be a consequence of metabolic syndrome, which in turn is associated with psoriasis"(98).
Recent studies by some renowned institutions suggested that green tea(99) and grape(100) may be the next generation of ingredient extracted from natural sources for reduced risk and treatment of psoriasis.
If you need more information of the above smoothie, please visits, The Unbelievable Smoothie Green Tea and Grape for reduced risk and Treatment of Psoriasis(101).
The complications
1. Tophi
Tophi is a forming of lumps building up around the joint due to chemical called uric acid. According to the University Hospital Southampton NHS Foundation Trust, tophi may be managed and treated by non-surgical and surgical procedures(102).
Allopurinol, the conventional medication, allopurinol (100 to 600 mg daily) expressed low- to moderate-quality evidence indicating similar effects on withdrawals due to adverse events (AE) and serious adverse events (SAE). and incidence of acute gout attacks in randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs)(103). And benzbromarone is probably more successful than probenecid at achieving serum urate normalisation in people with gout(104).
According to the Hospital General Universitario de Alicante, diet supplements of vitamin C, has shown to the attenuated forming of lumps on joints but the study did not assess tophus regression, pain reduction or disability or health-related quality of life impact. The study reported no adverse events and no participant withdrawal due to adverse events(105).
Furthermore, there is good evidence from observational studies of an association between various lifestyle risk factors and gout development but the The Royal Melbourne Hospital, Parkville, Australia study did not include the expression of physical function, tophus regression and serum urate normalisation(106).
2. Kidney stone
Kidney stone is a composed of mineral salts formed in the kidneys. Men account for the 80% of those with kidney stones and are at risk of the forming between 30 and 40 years of age. About 75% of kidney stones are calcium stones.
Minimally surgical intervention depends on performing the least invasive technique with the highest success of stone removal, according to Harvard Medical School(107). Others suggests that flexible ureterorenoscopy may be the first-choice treatment for stones <2cm(108).
Dr. Ahmed MH and colleagues at the Milton Keynes Hospital NHS Foundation Trust, believe that Renal stone disease and gallstone disease are the widely prevalent renal stone disease and gallstone disease across the globe, are associated with a variety of diseases including gout(110).
In a total of 396 male patients with gout and 403 age- and sex- matched healthy controls included in this study conducted by the Affiliated Hospital of Qingdao University, risk of renal calculus is increased in patient carrying the TT genotype of CARD8 rs2043211 polymorphism with gout(109).
Recent study by some well known institution suggested that the combination of Green tea(111), Grape (112) and Sweet Potato(113) smoothie may hold a key in further studies in production of an effective natural ingredients for prevention and treatment of kidney Stones without inducing adverse effects.
If you need more information of the above smoothie, please visits, The Best Smoothie of Green tea, Grape and Sweet Potato for Prevention and Treatment of Kidney Stones caused by Medullary sponge kidney(114).
3. Joint damage
Acute gout or acute gouty arthritis can induce joint damage thoough deposit of uric acid crystals in joint spaces. Patients with gout are associated to complication of joint damage, according to the joint study led by University of Auckland, monosodium urate crystals are frequently present in joints affected by radiographic damage in gout(115).
Dr. Dalbeth N and professors at the University of Auckland in the review of joint damage in aptients with gout, suggested that intensive urate-lowering therapy plays a critical role in improvement in structural damage, particularly bone erosion(116).
MDHAQ (Multidimensional Health Assessment Questionnaire) scores for physical function (FN), pain, Patient Global Estimate (PATGL), and RAPID3 (Routine Assessment of Patient Index Data, a composite of these 3 measures) in the examination of patients with osteoarthritis, systemic lupus erythematosus, spondyloarthropathy, and gout, similarly to rheumatoid arthritis suggested an improvement scores in patients with 5 diagnoses, according to NYU Hospital for Joint Diseases,(117).
4. Recurrent gout
Recurrent episodes of gout have shown to induce further damage to joints and other tissues from urate crystal deposition. Certain medication such as aspirin used on two consecutive days is associated with an increased risk of recurrent gout attacks(118). Purine-rich foods intake is associated to increased risk of recurrent gout after 2 days(119).
Consumption of beer, loop or thiazide diuretics, ciclosporin, tacrolimus, ethambutol, pyrazinomide, nicotinic acid, also are found stimulate the progression of recurrent gout, according to Dr. Robin Fox, GP(120). Other risk factors for recurrent gout include medical conditions such as Psoriasis Myeloproliferative disorders, Administration of cytotoxic drugs (tumour lysis syndrome), Inherited enzyme deficiencies and Lead poisoning(occupations)(120).
Fortunately, in a study of 633 individuals with gout. cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks. Cherry extract intake showed a similar inverse association(121). And according to the University of Maryland School of Medicine, "primary prevention of gout can be achieved through lifestyle changes including weight loss, restricting protein and calorie intake, limiting alcohol consumption, avoiding the use of diuretics in the treatment of hypertension, and avoiding occupational exposure to lead"(122).
5. Advanced gout
Untreated gout may cause even more deposits of urate crystals to form under the skin in nodules called tophi (TOE-fie), leading to advanced gout with tophi developed in several areas, including fingers, hands, feet, elbows,.......Occasionally,untreated gout can lead to advanced arthritic changes. and chronic discomfort of the hallux MTPJ, necessitating surgical intervention to help alleviate symptoms, according to Dr. Balutis E and Dr., Pino A.(123).Refractory gout in patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl were treated successfully with long-term pegloticase treatment, improvements in clinical status, in the form of flare and tophus reduction and maintained goal range urate-lowering responses during up to 2.5 years of additional treatment(124).
The Diagnosis
According to the Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Feb. Report No.: 15(16)-EHC026-EF.AHRQ Comparative Effectiveness Reviews(125).
if you are experience SHARP pain in the joint with visual symptoms of collection of urate crystal deposit and other clinical signs and symptoms of gout, your doctor may order the below tests
1. Joint fluid test
Withdraw fluid from affected joint to test for sign of urate crystal accumulation for confirmation of gout.
2. Blood test
Blood test is necessary to measure levels of uric acid for gout and creatinine for kidney function in your blood. According to the University of Auckland, measured blood test in people with gout has caused confusion about the details of urate measurement in suboptimal care(126), as the measurement may not be accurate as some some people with high levels of uric acid levels, have never experienced gout. And some people have signs and symptoms of gout, but don't have higher levels of uric acid in their blood(127).
3. X-ray imaging(125)
The aim of the test is to rule other causes of inflammation of joints. In case of negative or inconclusive, other tests such as ultrasound and dual energy CT scan to provide additional information in patients(128),
4. Ultrasound(125)
The aim is to detect any urate crystals deposit in a joint or in a tophus for confirmation of gout when X ray is inconclusive and negative(128). Dr. Codreanu C and Dr. Enache L said, "adding US to the clinical and serological features will significantly improve the sensitivity of proposed criteria. The ability of high resolution US to detect crystalline deposits of monosodium urate in joints and soft tissues is well recognized"(129)
5. Dual energy CT scan(125)
The aim of the test is to detect any any urate crystals deposit in a joint or in a tophus even without sign of acute inflammation. "Dual-energy computedtomography (CT) contributes over conventional single-energy CT,........ Particular emphasis will be placed on acute gout, bone marrow edema, acute renal colic, acute cardiovascular and neurovascular emergencies aswell as characterization of abdominal incidentalomas" according to the joint study led by the University of British Columbia.
The Misdiagnosis and delay diagnosis
According to the University of Kansas School of Medicine, out of 9,108 consecutive new patients seen in an outpatient rheumatology clinic, 155 (1.7%) diagnosed as having gout, 164 (1.8%) had been incorrectly diagnosed as having gout in the community(131).
"The main factors potentially contributing to delayed diagnosis after consultation included reported misdiagnosis, attacks in joints other than the first metatarsophalangeal joint, and female gender. The limitations in using serum uric acid (SUA) levels for diagnostic purposes were not always communicated effectively to patients, and led to uncertainty and lack of confidence in the accuracy of the diagnosis", the Keele University insisted(134).
1. Rheumatoid arthritis
In elderly, polyarticular gout may be misdiagnosed due to confusing clinical presentation of "diuretic gout" such as polyarticular onset, subacute symptoms. ......According to the Albert Einstein College of Medicine, misdiagnosis of rheumatoid arthritis can induce poor treatment of gout, affecting underlying conditions of renal insufficiency, and cardiac risks(132).
2. Elderly-onset gout (EOG)
Elderly-onset gout (EOG) is a condition of gout with onset at age 65 years or over, shared a relevant epidemiological, clinical and therapeutic differences from the typical middle-age form. According to the University of Ferrara,"EOG has recently been confirmed as the most common inflammatory arthropathy in older people, with important demographic implications and substantial impact on daily clinical practice. Despite the high prevalence, gout, in the elderly, often remains misdiagnosed or diagnosed late in its clinical course."(133).
3. Misdiagnosis due to confusing in classification
According to the Hospital Universitario Cruces, as a step-up disease, gout consists different stages: acute gout, intercritical gout, and chronic gout but in clinical practice, gout should be considered as a single disease with either or both acute (most commonly, episodes of acute inflammation) but not restricted to chronic synovitis in support the clinical manifestations and diagnosis of gout(135).
4. Recurrent gouty arthritis
There is a report of misdiagnosis of recurrent gouty arthritis associated with hyperuricemia and hyperlipidemia during adolescence. as steatohepatitis in a family with mild glycogen storage disease type 1a. National Chung Hsing University, due to the effect of result of misdiagnosis suggested that patients with mild glycogen storage disease should be considered in the adolescents with unexplained hyperuricemia and hyperlipidemia, despite the presence of normal blood glucose levels(136).
5. Chylous cysts of the neck or chest
According to the Geisinger Medical Center, there is a report of chylous cyst was misdiagnosed as recurrent chest wall gouty tophus due to form birefringent crystals upon drying(137).
6. Psoriatic arthritis
In the review of Forty-two patients with psoriatic arthritis who were referred to a tertiary medical center from 1983 to 1987, eight patients with foot and ankle involvement were diagnosed and treated for either gout or compression of a digital nerve due to failure to identify psoriatic skin lesions and the associate foot and ankle symptoms with psoriatic arthritis.(138).
The Prevention and Management
The Do’s and Do not’s list
1. Coffee
Researchers found that long-term moderate coffee consumption is associated with a lower risk of incident gout, particular in women(139). According to the joint study led by the Naresuan University Hospital, there is an associations between vitamin C, alcohol,coffee, tea, milk and yogurt with uric acid and the risk of gout(140).
In Japanese men and women aged 49-76 years, "There were inverse associations of coffee consumption with serum UA concentrations and hyperuricemia in men regardless of adjustment for covariates" Said by Dr. Pham NM and colleagues at the Kyushu University(141).
2. Maintaining adequate fluid intake, particular at night
Dehydrate is associated with the increased risk of gout, particular at night time, epidemiological study suggested(142). Drinking water or skim milk can improve gout control, according to findings from two studies that highlight the important contribution of lifestyle factors on gout prevention and management(144), and recent use of diuretics is associated with a significantly increased risk for recurrent gouty arthritis(143).
3. Weight reduction
Obesity cause cause pressure to the joint. Obesity is not only a risk factor for incident gout but is associated with an earlier age at gout onset(147). According to the a total of 543 cases of juvenile gout from the Ho-Ping Gout Database and 5269 gouty cases with onset age of 40 to 50 years, family history of overweight and hereditary background are significantly associated to increased risk of juvenile gout(145).
Dr. Lee J and the research team at the The Catholic University of Korea, said," Gout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities."(146).
In deed, women with early- and mid-adult life obesity, high mid-adult life waist-to-hip ratios, and adulthood high weight gain, experience a greater incidence of gout, according to Johns Hopkins University School of Medicine(148).
4. Dietary and life style pattern changes
a. Reduce alcohol
Alcohol intake is strongly associated with an increased risk of gout. This risk varies substantially according to type of alcoholic beverage: beer confers a larger risk than spirits, whereas moderate wine drinking does not increase the risk(150). The association between excessive alcohol consumption and risk of gout has been suspected since ancient times which was confirmed by the study by the Harvard Medical School, Boston(149).
Unfortunate to alcohol drinker, regardless of type of alcoholic beverage, episodic alcohol consumption,was associated with an increased risk of recurrent gout attacks, including potentially with moderate amounts(151).
b. Reduce intake of foods with high levels of purine, such as sardines, herring, kidney and sweetbreads, shrimp, etc.(152). According to the Third National Health and Nutrition Examination Survey, in the review of the data from 14,809 participants (6,932 men and 7,877 women) ages 20 years and older for the years 1988-1994, higher levels of meat and seafood consumption are associated with higher serum levels of uric acid(153) and sugar-sweetened soft drink consumption is associated with serum uric acid levels and frequency of hyperuricemia(154).
c. Diet with foods to prevent gout
Dairy products, vegetables, nuts, legumes, fruits (less sugary ones), and whole grains are healthy choices for the comorbidities of gout and may also help prevent gout by reducing insulin resistance(156). Coffee and vitamin C(155) supplementation could be considered as preventive measures as these can lower urate levels, as well as the risk of gout and some of its comorbidities(156).
Diet with foods such as cherries and strawberries to prevent gout(157), as evidence of the impact of strawberry intake on gout has been report(157).
5. Reduce intake of medications which can cause gout and recurrent gout by reviewing them with your doctor, as certain medicine such as Thiazide and loop diuretics(158).
6. Exercise
Regular physical exercise is associated to reduce risk of gout(159).
“Exercises to relieve gout should be done steady and cautiously as to avoid further irritation to the joints. The best exercises for gout are range of motion types: strength training, stretching and building endurance. Yoga is an exercise that incorporates all four; however, there are other exercises that can be done individually also” According to the article of How to Exercise If You Have Gout(160).
The top anti inflammatory Foods
The top 5 anti inflammatory foods in reduced risk of over expression of pro inflammatory cytokine are always important to prevent the early onset and patient with gout as well as the expression of cardiovascular and renal risks(190).
2.1. Garlic
Inflammation plays an important roles in the early onset of uric acid involved the develop of gout. Dr. Perez-Ruiz F and Dr, Becker MA suggested, inflammation may provide a mechanistic explanation, related to some important chronic co-morbidities remains uncertain(189).
According to the joint study led by the Instituto de Neurobiología, alliin, a garlic (Allium sativum) compound inhibited the exprssion of LPS-induced inflammation(186) in 3T3-L1 adipocytes(187), involved decreasing serum levels of glucose, insulin, triglycerides, and uric acid, as well as insulin resistance, and cytokine levels(187).
Dr. Percival S. said, "Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification"(188).
2.2. Turmeric
Turmeric with the similar property as garlic in enhancing immune system fighting against inflammation caused by either free radicals and foreign invasion(191). Recent study suggested, IL-1β inhibited by turmeric(195) is a potent proinflammatory cytokine of the innate immune system involved in host defense against infection. may increase production of IL-1β which plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout(194).
In animal with gout study, there was a positive correlation between intra-articular macrophage migration inhibitory factor involved in increased synovial fluid of patients with acute gout and IL-1β concentration(196).
According to the joint study led by the Federal University of Technology and China Pharmaceutical University, turmeric (Curcuma longa) exhibited effects on enzyme activities of purinergic and cholinergic systems as well as inflammatory cytokine levels(192). including including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)(192) through inhibiting the xanthine oxidase (XOD) activity related to amelioration of urinary uric acid (Uur) level(193).
2.3. Green Tea
Green tea, a precious drink in traditional Chinese culture has been served exceptional in socialization for more than 4000 thousand years. Due to its commercial values and health effects, green tea now was cultivated all over the world in suitable climate. According to the Naresuan University Hospital, dietary of green tea is associated to attenuate risk of of yugout(197), through its effect on lower SUA level and decreases uric acid clearance via significantly elevated serum antioxidant capacity(198).
Dr. L'Allemain G said, in the study of the effect of Epigallo catechin-O-gallate (EGCG), the most active epicatechin in green tea, "although no direct molecular target has been so far elucidated for EGCG, the multi-potentialities of this molecule, along with its broad bioavailability, render it very attractive as a putative curative drug for various diseases such as dermatosis, gout, atherosclerosis and cancer" and "Its anti-oxidant properties could explain its antagonistic action in some inflammatory processes"(199)
2.4. Shiitake mushroom
Shiitake mushroom is an edible mushroom, genus Lentinula, belongings to family Marasmiaceae, native to East Asia and widely cultivated for consumption for its health benefits and commercial purpose in many Asian countries. According to the joint study led by the University of Florida, intake of Shiitake mushroom improved immunity, through cell proliferation and activation and increased sIgA production, reduced inflammation via cytokine and serum CRP levels(200). Dr. Urano W and colleagues at the Tokyo Women's Medical University said, "Decrease in SUA during acute gouty arthritis is associated with increased urinary excretion of uric acid; an inflammatory process may play a role in the mechanism"(201).
The effect of Shiitake mushroom on Interleukin-6 (IL-6), a monokine with a number of biological activities, are intimately related to inflammatory responses in ameliorated serum uric acid (SUA) and increased uric acid excretion(201)(202).
2.5. Onion
Onion is a plants in the genus Allium, belongings to the family Alliaceae, a close relation of garlic. It is often called the "king of vegetables" because of its pungent taste and found in a large number of recipes and preparations spanning almost the totality of the world's cultures. According to the Universidad Nacional de Cuyo, garlic (G) and onion (O) exhibited anti-inflammatory properties through antioxidant in attenuated oxidative stress(203) as well as (poly)phenols altered cytokine release, in protection against age-related inflammation and chronic diseases, including gout(204).
In fact, Quercetin, a flavonoid found in high levels in onions lowers blood uric acid in humans in 4 weeks, in dose dependent-manner, according to a randomised, double-blinded, placebo-controlled, cross-over trial.(205).
2.6. Ginger
Ginger is the genus Zingiber, belongings to the family Zingiberaceae, native to Tamil, used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc. According to the VIT University, Trikatu, a herbal compound including ginger exhibited significant analgesic, anti-pyretic and anti-inflammatory effect against gout through precipitation of monosodium urate crystals in the joints(206).
Dr. Sabina EP and professors also at the VIT University, in the evaluation of 6-Shogaol isolated active principle from ginger suggested that application of 6-Shogaol attenuated the increased significantly the levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha and paw volume and improved the activities of anti-oxidant status in monosodium urate crystal-induced mice(207).
The Top immune enhancers
Enhancing immunity has shown to reduced risk of inflammatory diseases(218). The University of Calgary study insisted "Uric acid crystals [monosodium urate (MSU)] have emerged as an important factor for both gouty arthritis and immune regulation. This simple crystalline structure appears to activate innate host defense mechanisms in multiple ways and triggers robust inflammation and immune activation"(219)
1. Omega 3 fatty acids
Omega-3 fatty acids, phytochemincals in the class of Lipids, found abundantly in dark-green leafy vegetables, grains, legumes, nuts, etc. play an impotant role in reduced risk of weaken immunity inducing inflammatory diseases, including gout(220). Dr. Simopoulos AP said, "omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities," and "Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases."(221).
Omega 3 fatty acid for prevention of hyperlipidemia(223) may also be effective in reduced metabolic syndrome including hypertension, hyperuricemia, hyperinsulinemia......., according to the St. Thomas' Hospital, (222).
2. Selenium
Selenium is one of most powerful antioxidant, played an important role in enhancing immune system fighting against forming of free radicals and foreign invasion, epidemiological evidences suggested.
In the follow up of serum selenium (Se) concentrations in 117 hemodialysis patients (HPs) during a 2-year longitudinal study, the University of Granada found that dyslipidemia and hyperuricemia found have a negative correlation between the serum Se and uric acid levels(224).
The observation of total antioxidant capacity, including selenium was significantly higher in non-responders and well correlated with hyperuricemia(225).
3. Zinc
Zinc may plays an important role for the development of osteoarthritis, according to Randers Regional Hospital, patient with osteoarthritis are found to have significantly higher serum zinc concentrations and lower urine zinc concentrations in comparison to patient with osteoporosis(226).
In Gout, Zinc stimulates insulin action and insulin receptor tyrosine kinase activity in patient with type II diabetes reducing the risk of Insulin resistance induced the complication of hyperuricaemia(227).
Furthermore, according to the Universidade Federal de São Paulo, zince supplement decreased insulin resistance, anthropometric and diet parameters, leptin and insulin concentration, zinc concentration in the plasma and urine, lipid metabolism and fasting plasma glucose, affecting the hyperuricaemia levels in type II diabetes(228).
4. Vitamin B2
Vitamin B2, awater soluble, also known as riboflavin has a chemical compound formula of C17H20N4O6. Like many other vitamin B complexes, it plays an important role in providing energy to our body by the metabolism of fat, carbohydrates and protein. According to the joint study led by National Cancer Center, vitamin B2 levels were significantly lower in the hyperuricemia subjects than in the controls, in the study of 28,589 people who participated in a health examination between 2008 and 2011(229) due to higher alcohol intake and lower vegetable and dairy product intake.
A Australian Diabetes, Obesity and Lifestyle Study 1999/00 (n=9734, age 25-91) and Tromsø Study 4 1994/95 (n = 3031, age 25-69).suggested, " lower levels of SUA were found in subjects with higher consumption of carbohydrates, calcium and vitamin B2, while higher fat intake was associated with higher SUA"(230).
5. Vitamin B6
Vitamin B6 is water soluble and a member of vitamin B complex, played an important role in amino acids metabolism for to maintaining the proper function in our body. Vitamin B6 deficiency may be associated to risk of hyperglycaemia and hyperuricaemia(231). In deed, according to the Universidad Complutense de Madrid, consumption of Cereals, vegetables, legumes and fruit, together with milk and eggs, constituted the most important ingredients of the diet in a closed community showed to reduced risk of deficiencies of iron, magnesium, zinc, vitamin B(6) and vitamin D in induction of hyperuricaemia, the main cause of gout(232).
The diet
Dietary consumption and life style plays an important role in association to risk and attenuated risk and progression of gout(208)..
1. Green tea
Green tea containing more amount of antioxidants than any drinks or food with the same volume, is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Regular intake of green tea has shown to reduced levels of uric acid by epidemiological and research studies and literature(210)
Recent study suggested that green tea exhibited anti SUA level and induced decreases uric acid clearance in a study comprised 1-week control, 2-week interventional, and 1-week follow-up periods conducted by the Chiang Mai University(209).
2. Coffee
Coffee is a brewed drink prepared from roasted coffee beans from the Coffee plant. The third national health and nutrition examination survey. using data from 14,758 participants ages >/=20 years in (1988-1994) support the effectiveness of drinking coffee >/=6 cups daily in ameliorated risk of gout in comparison to green tea. The study also said, "The inverse association with coffee appears to be via components of coffee other than caffeine"(211).
According to a system review by the joint study led by the Ajou University School of Medicine, moderate coffee intake might be advocated for primary prevention of hyperuricemia and gout in both genders(212).
Dr. Pham NM and colleagues at the Kyushu University said, " There were inverse associations of coffee consumption with serum UA concentrations and hyperuricemia in men regardless of adjustment for covariates. Women showed a statistically significant, but weaker, inverse association betweencoffee and serum UA levels after allowance for the confounding factors"(213).
3. Yogurt
Yogurt, a product of dairy used widely in Western world as a healthy foods for enhancing the digestive system is a dairy product made from milk. According to Dr. Towiwat and , Li ZG in the review of dietary effect of yogurt insisted that yogurt expressed anti uric acid and reduced risk of gout in regular consumption(214).
Dr Schlesinger said, " Non-fat milk and low-fat yogurt have a variety of health benefits and dairy products may have clinically meaningful antihyperuricaemic effects"(215) and "Dairy consumption was inversely associated with the serum uric acid level." Harvard Medical School, showed(216).
4. Milk
The diary product produced from cow drunk by millions of the world population may also have a positive effect on gout(216). According to the 3-month randomised double-blind controlled trial of milk products for prevention of gout flares, consumption of SMP/GMP/G600 daily over the 3-month period, showed greater improvements in pain and fractional excretion of uric acid, particular in tender joint count(217).
The Phytochemicals to prevent Gout
1. Quercetin and Rutin
Quercetin is a plant pigments belongings to the group of flavonoids and its conjugate rutin is a quercetin-3-O-rutinoside and sophorin, according to Dr. Zhu JX and research team at the School of Life Sciences, Nanjing University expressed inhibition of enzyme activities in mouse liver in relation to their absorption and metabolism, and their potential application to treat gout and hyperuricemia(161). Dr. Shi Y and Dr. Williamson G said" quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95 % CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure" in a randomised, double-blinded, placebo-controlled, cross-over trial(162). The antioxidant also exerted a strong anti-inflammatory effect that may be useful for the treatment of acute gouty arthritis, TianJin University of Traditional Chinese Medicine(163)
2. Morin
Morin (3,5,7,2′,4′-pentahydroxyflavone), a phytochemical found in the twigs of Morus alba L. documented in traditional Chinese medicinal literature to treat conditions akin to gout, was demonstrated to exert potent inhibitory action on urate uptake in rat renal brush-border membrane vesicles(164). In the study of Ramulus Mori, the branch of Morus alba, is widely used in traditional Chinese medicine prescriptions to treat gout and hyperuricemia, researchers at the Nanjing University suggested that the effectiveness of the herbal medicine in treating gout, probably due to the presence of antioxidants, including morin(165).
According to the Nanchang University, luteolin exhibited a stronger synergistic effect with kaempferol than did morin at the lower concentration(166).
3. Other phytochemicals
13 flavonoids including myricetin, kaempferol, icariin, apigenin, luteolin, baicalin, silibinin, naringenin, formonoetin, genistein, puerarin, daidzin and naringin dihydrochalcone selected to investigate for their hypouricemic action in mice, also significantly reduced liver uric acid level in hyperuricemic animals(167).
3.1. Myricetin
Myricetin is one of the flavonoid class of polyphenolic compounds, found abundantly in fruits and vegetables, including berries.
According to Dr. Li Y and colleagues, Myricetin and luteolin expressed binding to the xanthine oxidase and cyclooxygenase-2 in attenuate the complex pathogenesis of gout, a metabolic disease(168). The Sri Ramakrishna Institute of Paramedical Sciences study also exhibited the protective effect of asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein in reduced the expression of in gout patients(169).
In support of the effectiveness of flavonoids for treatment of gout, Universidad Nacional de Asunción insisted that quercitrin, quercetin, myricitrin and myricetin strongly displayed the xanthine oxidase inhibitory action against the over expression of gout(170).
3.2 Kaempferol
Kaempferol is one of the flavonoid class of polyphenolic compounds, found abundantly in fruits and vegetable with formula C15H10O6. According to the Nanchang University, the phytochemical catalyze xanthine to generate uric acid and cause hyperuricemia and gout, through it direct interference of site of Xanthine oxidase (XO), a key enzyme in purine catabolism(171).
Dr. Ahmad NS and colleagues at the National University of Sciences and Technology suggested that kaempferol-3-O-beta-d-glucopyranoside isolated from Pistacia integerrima leaves, exhibited dose dependent UA lowering effect in hyperuricemic mice(172).
3.3 Icariin
Icariin, a flavonol glycoside, type of flavonoid is a 8-prenyl derivative of kaempferol 3,7-O-diglucoside. According to the Nanjing University, icariin exhibited anti hyperuricemic and over expression of gout effects through inhibition on the liver xanthine oxidase (XOD) activities(167).
3.4. Apigenin
Apigenin, a natural product belonging to the flavone class, remarkedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse, according to the study by the Beijing Institute of Pharmacology & Toxicology(173). Apigenin-7-O-β-D-glucoside, derivative of apigenin isolated from Olea europaea leaf (Ph.Eur.) extract, exhibited strongly the anti-gout property through expression of inhibitory effects on xanthine oxidase (XO)(174).
3.5. Luteolin
According to Dr. Li Y and colleagues, Myricetin and luteolin expressed binding to the xanthine oxidase and cyclooxygenase-2 in attenuate the complex pathogenesis of gout, a metabolic disease(168).
The Antioxidants
Dr. Choi HK in the study of dietary risk factors for rheumatic diseases said, "Because diet is an unavoidable universal exposure for people, even a small effect that can be achieved by dietary manipulation may produce a large impact on the population's health" and "A recent prospective study investigated several purported dietary factors for gout and confirmed some of the long-standing suspicions (red meats, seafood, beer, and liquor), exonerated others (total protein, wine, and purine-rich vegetables), and also identified potentially new protective factors (dairy products)"(185).
1. The Free radical scavengers
1.1. Vitamin A
Vitamin A, a bi-polar molecule formed by bonds between carbon and hydrogen, is a fat soluble vitamin, which can not be stored in the live, converted from beta-carotene, a powerful antioxidant.
According to the Arthritis Research Centre of Canada, Vancouver, the finding of vitamin A and its derivative in reduced risk and treatment has been controversial as vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas β-carotene intake may be beneficial against hyperuricemia(175) by using data from 14,349 participants ages ≥20 years i